The recent advances in nanotechnology and nanofabrication of semiconductor materials present themselves with new opportunities for miniaturized, ultra-sensitive, label-free, and parallel sensors capable of rapid and highly accurate analysis of biological and chemical entities. Silicon nanowire sensors, based on field effect modulation of current upon binding of molecules on the nanowire surface, have been successfully demonstrated for the detection of DNA and proteins in fluids on individual devices. However, these devices are still to be realized in an array format, in a robust manner using top-down fabrication techniques, with detection of multiple molecules. In this R21 proposal, we have assembled an interdisciplinary team with the goal of designing, producing, functionalizing, and testing the silicon nanowire sensor array. Our work will be motivated by, (a) the need to detect single stranded DNA molecules for sensing and diagnostic applications, and (b) detect microRNA (miRNA) from cell lysates, which have been recently shown to be indicative of diseases such as cancer. These goals will be accomplished by our team of researchers with expertise in nano-scale computation (Ashraf Alam), novel linker design and surface chemistry (Donald Bergstrom), and micro/nano-fabrication (Rashid Bashir). The following are the specific aims of the project: (i) Use novel nanoscale computation approaches to guide the design and fabrication of the nano-wire sensor elements, (ii) Develop novel top-down silicon fabrication techniques to produce nano-wire arrays within microfluidic devices, (iii) Develop novel techniques to functionalize the individual sensors in an array using laser or electrically mediated thermal exchange reactions, and (iv) Perform the detection experiments in an array of nanowires within a microfluidic biochip and explore the use of nano-particle (dendrimer) based charge amplification schemes. Each specific aim includes novel and innovative state-of-the-art nanoscale research with broad applications in the area of Nanobiotechnology. [unreadable] [unreadable] [unreadable]